The mitochondria have an independent genetic system of DNA (mtDNA) and RNA and are therefore able to synthesise certain proteins on their own. Both genes of the cell nucleus and the mitochondrial genome code for the components of oxidative phosophorylation and the citrate cycle. A genetic defect of the mtDNA may therefore affect oxidative phosphorylation and the citrate cycle, respectively, and cause malfunctions. Such defects or malfunctions have been associated with the so-called mitochondrial diseases.
Genetic defects of mtDNA may be the result of local mutation by which one base is replaced by another. Such point mutations are associated with neurogenetic myasthenia, ataxia and retinopathia pigmentosa, for example.
Genetic defects of the mtDNA may also be caused by insertion or deletion mutation where one or more nucleotides are inserted into or deleted from the DNA. This mutation mechanism is being discussed in connection with the Kearns Sayre syndrome and the Pearson syndrome.
The mutation of mtDNA also plays a role in neurodegenerative diseases such as Parkinson syndrome, Alzheimer's disease or Chorea Huntington disease (Encyclopedia of Molecular Biology and Molecular Medicine, Vol., 4, Ed. R. A. Meyers). However, it has not been possible to allocate the causative mutations to these diseases without any doubt so far. For example, an accumulation of mutations is also being discussed as a basis of pathogenesis.
The Parkinson syndrome exhibits a number of symptoms which may be divided into three groups. Motoric disorders are expressed by the plus symptoms rigor (increased tonus of the striated musculature) and medium to heavy tremor (twitching in rapid succession) and the minus symptom hypokinesia or akinesia (deterioration of the motor system, loss of postural reflexes). Vegetative symptoms (increased flow of saliva and tears, post-encephalitic seborrhoea) and psychic disorders (increased indecisiveness, depressive moods, etc.) are also being observed.
The disease is based on a destruction of nerve cells in the motoric key areas of the brain stem. In Germany, for example, about 200,000 patients are affected. At molecular level, the Parkinson syndrome is associated, among other things, with mutations of the mitochondrial genome. It has been possible to show mtDNA deletions in Parkinson patients. In addition, a dopamine insufficiency of certain regions of the brain is found in cases of Parkinson syndrome. The symptoms observed are an expression of the impaired balance between the neurohumoral transmitter substances acetyl choline and dopamine.
At present, drug therapies are based on the inhibition of cholinergic neurotransmission with centrally acting anticholinergics, the increase of the dopamine concentration by administration of the dopamine precursor Levodopa and the stimulation of central dopamine receptors with direct dopaminergic agonists.
Specific therapies therefore comprise the administration of anticholinergics or of Levodopa. In order to favourably influence both the plus symptoms and the minus symptom in Parkinson patients, a combination therapy is usually required which is supplemented by non-drug therapeutic measures.
On the other hand, a therapy with anticholinergics is inadvisable for Parkinson patients already suffering from marked psycho-organic disorders or exogenpsychotic symptoms, because a worsening of the symptoms must be expected.
Side effects limiting the therapeutic use of Levodopa are motoric symptoms (hyperkinesia, dyskinesia), vegetative disorders (gastro-intestinal problems, among others) and cardiovascular disorders (such as orthostatic disorders).
Alzheimer's disease is pre-senile or senile dementia which progresses irreversibly and which is characterised by the destruction of areas of the brain. Recent studies show that, in addition to mitochondrial genetic defects, the increased presence of the apolipoprotein E4 (apo E4) is related to the occurrence of Alzheimer's disease. In the hereditary form of this disease, the corresponding gene for the apo E4 is often defective. As opposed to the Parkinson syndrome, no therapy other than treatment with indomethacin is available for Alzheimer's disease. However, indomethacin also has considerable side effects.
Retinopathia pigmentosa is a degenerative process which is more often hereditary than acquired. It is associated with a narrowing of the retinal vessels, opticus atrophy, the destruction of neural elements of the retina and a deposition of pigments. Symptoms are nyctalopia, a severe narrowing of the field of vision and loss of sight.
Mitochondrial encephalomyopathy is a disease characterised by disorders of the mitochondrial respiratory chain. Typical symptoms are myopathy (so-called ragged red fibres myopathy), stunted growth, dementia, epileptic episodes, ataxia, focal neurological disorders and MELAS (mitochondrial encephalomyopathy, lactate acidosis and strokes).
Chorea Huntington is a hereditary dominant autosomal disease with a defect on the short arm of the 4th chromosome which usually becomes manifest between the ages of 30 and 50 and is associated with progressive dementia. A defect or atrophy of the nucleus candatus and possibly the nucleus lentiformis may be named as possible causes. A defect of the neurotransmitter metabolism and the influence of mtDNA defects are under discussion.